tbuckley/cabot-search huggingface dataset:
The complex network of transcription factors, immune checkpoint inhibitors and stemness features in colorectal cancer: A recent update
Authors: Maysaloun Merhi, Fareed Ahmad, Nassiba Taib, Varghese Inchakalody, Shahab Uddin, Alaaeldin Shablak, Said Dermime
Journal: Seminars in Cancer Biology (2023)

Cancer immunity is regulated by several mechanisms that include co-stimulatory and/or co-inhibitory molecules known as immune checkpoints expressed by the immune cells. In colorectal cancer (CRC), CTLA-4, LAG3, TIM-3 and PD-1 are the major co-inhibitory checkpoints involved in tumor development and progression. On the other hand, the deregulation of transcription factors and cancer stem cells activity plays a major role in the development of drug resistance and in the spread of metastatic disease in CRC. In this review, we describe how the modulation of such transcription factors affects the response of CRC to therapies. We also focus on the role of cancer stem cells in tumor metastasis and chemoresistance and discuss both preclinical and clinical approaches for targeting stem cells to prevent their tumorigenic effect. Finally, we provide an update on the clinical applications of immune checkpoint inhibitors in CRC and discuss the regulatory effects of transcription factors on the expression of the immune inhibitory checkpoints with specific focus on the PD-1 and PD-L1 molecules.
Identification of a Genetic Susceptibility Locus for Idiopathic Pulmonary Fibrosis in the 16p Subtelomere Using Whole-Genome Sequencing
Authors: Lauren J. Donoghue, Amy D. Stockwell, Margaret Neighbors, Rebecca X. Sheng, Ramanandan Prabhakaran, Paul J. Wolters, Lisa H. Lancaster, Jonathan A. Kropski, Timothy S. Blackwell, Mark I. McCarthy, Brian L. Yaspan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Identification of a Genetic Susceptibility Locus for Idiopathic Pulmonary Fibrosis in the 16p Subtelomere Using Whole Genome Sequencing." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
MYB insufficiency disrupts proteostasis in hematopoietic stem cells, leading to age-related neoplasia
Authors: Mary L. Clarke, Roza B. Lemma, David S. Walton, Giacomo Volpe, Boris Noyvert, Odd S. Gabrielsen, Jon Frampton
Journal: Blood (2023)

MYB plays a key role in gene regulation throughout the hematopoietic hierarchy and is critical for the maintenance of normal hematopoietic stem cells (HSC). Acquired genetic dysregulation of MYB is involved in the etiology of a number of leukemias, although inherited noncoding variants of the MYB gene are a susceptibility factor for many hematological conditions, including myeloproliferative neoplasms (MPN). The mechanisms that connect variations in MYB levels to disease predisposition, especially concerning age dependency in disease initiation, are completely unknown. Here, we describe a model of Myb insufficiency in mice that leads to MPN, myelodysplasia, and leukemia in later life, mirroring the age profile of equivalent human diseases. We show that this age dependency is intrinsic to HSC, involving a combination of an initial defective cellular state resulting from small effects on the expression of multiple genes and a progressive accumulation of further subtle changes. Similar to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteasomal activity and elevated proliferation indicators, followed by elevated ribosome activity in young Myb-insufficient mice. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation.
High-dose melphalan treatment significantly increases mutational burden at relapse in multiple myeloma
Authors: Mehmet Kemal Samur, Marco Roncador, Anil Aktas Samur, Mariateresa Fulciniti, Abdul Hamid Bazarbachi, Raphael Szalat, Masood A. Shammas, Adam S. Sperling, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, Aurore Perrot, Jill Corre, Philippe Moreau, Anjan Thakurta, Giovanni Parmigiani, Kenneth C. Anderson, Hervé Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2023)

High-dose melphalan (HDM) improves progression-free survival in multiple myeloma (MM), yet melphalan is a DNA-damaging alkylating agent; therefore, we assessed its mutational effect on surviving myeloma cells by analyzing paired MM samples collected at diagnosis and relapse in the IFM 2009 study. We performed deep whole-genome sequencing on samples from 68 patients, 43 of whom were treated with RVD (lenalidomide, bortezomib, and dexamethasone) and 25 with RVD + HDM. Although the number of mutations was similar at diagnosis in both groups (7137 vs 7230; P = .67), the HDM group had significantly more mutations at relapse (9242 vs 13 383, P = .005). No change in the frequency of copy number alterations or structural variants was observed. The newly acquired mutations were typically associated with DNA damage and double-stranded breaks and were predominantly on the transcribed strand. A machine learning model, using this unique pattern, predicted patients who would receive HDM with high sensitivity, specificity, and positive prediction value. Clonal evolution analysis showed that all patients treated with HDM had clonal selection, whereas a static progression was observed with RVD. A significantly higher percentage of mutations were subclonal in the HDM cohort. Intriguingly, patients treated with HDM who achieved complete remission (CR) had significantly more mutations at relapse yet had similar survival rates as those treated with RVD who achieved CR. This similarity could have been due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity.
Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma
Authors: Jonathan A. Coleman, Wesley Yip, Nathan C. Wong, Daniel D. Sjoberg, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Eugene K. Cha, Timothy F. Donahue, Eugene J. Pietzak, A. Ari Hakimi, Kwanghee Kim, Hikmat A. Al-Ahmadie, H. Alberto Vargas, Ricardo G. Alvim, Soleen Ghafoor, Nicole E. Benfante, Anoop M. Meraney, Steven J. Shichman, Jeffrey M. Kamradt, Suresh G. Nair, Angelo A. Baccala, Paul Palyca, Bradley W. Lash, Muhammad A. Rizvi, Scott K. Swanson, Antonio F. Muina, Andrea B. Apolo, Gopa Iyer, Jonathan E. Rosenberg, Min Y. Teo, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2023)

Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability.
Screening for monkeypox virus infections in men who have sex with men in a sexual health clinic in Hanoi, Viet Nam
Authors: Paul C Adamson, Hao Thi Minh Bui, Thomas Kesteman, Diep Thi Ngoc Nguyen, Thuong Thi Hong Nguyen, Tan Van Le, Rogier H van Doorn, Jeffrey D Klausner, Giang Minh Le
Journal: The Lancet Microbe (2023)
Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program
Authors: P McLaughlin, A J Grillo-López, B K Link, R Levy, M S Czuczman, M E Williams, M R Heyman, I Bence-Bruckler, C A White, F Cabanillas, V Jain, A D Ho, J Lister, K Wey, D Shen, B K Dallaire
Journal: Journal of Clinical Oncology (2023)

The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies.
Tooth number abnormality: from bench to bedside
Authors: Han Zhang, Xuyan Gong, Xiaoqiao Xu, Xiaogang Wang, Yao Sun
Journal: International Journal of Oral Science (2023)

Abstract Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Stable and Dynamic Multiparameter Monitoring on Chests Using Flexible Skin Patches with Self‐Adhesive Electrodes and a Synchronous Correlation Peak Extraction Algorithm
Authors: Ziyue Wu, Xueting Li, Zhijie Feng, Chunxue Wan, Ya Li, Tianyu Li, Qing Yang, Xinyu Liu, Miaoning Ren, Jiameng Li, Xue Shang, Xiangyu Zhang, Xian Huang
Journal: Advanced Healthcare Materials (2023)

Advances in wearable bioelectronics interfacing directly with skin offer important tools for non-invasive measurements of physiological parameters. However, wearable monitoring devices majorly conduct static sensing to avoid signal disturbance and unreliable contact with the skin. Dynamic multiparameter sensing is challenging even with the advanced flexible skin patches. This epidermal electronics system with self-adhesive conductive electrodes to supply stable skin contact and a unique synchronous correlation peak extraction (SCPE) algorithm to minimize motion artifacts in the photoplethysmogram (PPG) signals. The skin patch system can simultaneously and precisely monitor electrocardiogram (ECG), PPG, body temperature, and acceleration on chests undergoing daily activities. The low latency between the ECG and the PPG signals enables the SCPE algorithm that leads to reduced errors in deduced heart rates and improved performance in oxygen level determination than conventional adaptive filtering and wavelet transformation approaches. Dynamic multiparameter recording over 24 h by the system can reflect the circadian patterns of the wearers with low disturbance from motion artifacts. This demonstrated system may be applied for health monitoring in large populations to alleviate pressure on medical systems and assist management of public health crisis.
Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective
Authors: Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi
Journal: Clinical and Molecular Hepatology (2023)

Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.
Preparation of 2D Polyaniline/MoO<sub>3−</sub><i><sub>x</sub></i> Superlattice Nanosheets via Intercalation‐Induced Morphological Transformation for Efficient Chemodynamic Therapy
Authors: Tingting Hu, Baoli Xue, Fanqi Meng, Lu Ma, Yonghua Du, Shilong Yu, Ruquan Ye, Hai Li, Qinghua Zhang, Lin Gu, Zhan Zhou, Ruizheng Liang, Chaoliang Tan
Journal: Advanced Healthcare Materials (2023)

Abstract Organic intercalation of layered nanomaterials is an attractive strategy to fabricate organic/inorganic superlattices for a wide range of promising applications. However, the synthesis of 2D organic/inorganic superlattice nanosheets remains a big challenge. Herein, the preparation of 2D polyaniline/MoO 3− x (PANI/MoO 3− x ) superlattice nanosheets via intercalation‐induced morphological transformation from MoO 3 nanobelts, as efficient Fenton‐like reagents for chemodynamic therapy (CDT), is reported. Micrometer‐long MoO 3 nanobelts are co‐intercalated with Na + /H 2 O followed by the guest exchange with aniline monomer for in situ polymerization to obtain PANI/MoO 3− x nanosheets. Intriguingly, the PANI intercalation can induce the morphological transformation from long MoO 3 nanobelts to 2D PANI/MoO 3− x nanosheets along with the partial reduction of Mo 6+ to Mo 5+ , and generation of rich oxygen vacancies. More importantly, thanks to the PANI intercalation‐induced activation, the PANI/MoO 3− x nanosheets exhibit excellent Fenton‐like catalytic activity for generation of hydroxyl radical (·OH) by decomposing H 2 O 2 compared with the MoO 3 nanobelts. It is speculated that the good conductivity of PANI can facilitate electron transport during the Fenton‐like reaction, thereby enhancing the efficiency of CDT. Thus, the polyvinylpyrrolidone‐modified PANI/MoO 3− x nanosheets can function as Fenton‐like reagents for highly efficient CDT to kill cancer cells and eradicate tumors.
POLARized Risk for Local Recurrence on the Basis of Tumor Biology: Is It That Simple?
Authors: Mylin A. Torres
Journal: Journal of Clinical Oncology (2023)

Long supported by randomized trials, radiation is known to provide a significant relative reduction in locoregional recurrence risk (LRR) in patients with breast cancer treated with breast-conserving surgery. 1,24][5] Even knowing that the absolute benefit of radiation is small in a substantial number of patients at low baseline risk for LRR, it remains a significant challenge to accurately determine the need for radiation in individual patients after breast conserving surgery with precision.
Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase
Authors: Jeong-Ju Yoo, Soo Young Park, Ji Eun Moon, Yu Rim Lee, Han Ah Lee, Jieun Lee, Young Seok Kim, Yeon Seok Seo, Sang Gyune Kim
Journal: Clinical and Molecular Hepatology (2023)

The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.
Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of College of American Pathologists Guideline
Authors: Praveen Vikas, Hans Messersmith, Carolyn Compton, Lynette Sholl, Russell R. Broaddus, Anjee Davis, Maria Estevez-Diz, Rohan Garje, Panagiotis A. Konstantinopoulos, Aliza Leiser, Anne M. Mills, Barbara Norquist, Michael J. Overman, Davendra Sohal, Richard C. Turkington, Tyler Johnson
Journal: Journal of Clinical Oncology (2023)

The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.The CAP guideline was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations.The ASCO Endorsement Panel determined that the recommendations from the CAP guideline, published on August 3, 2022, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer.Within the guideline, MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are all recommended testing options for colorectal cancer, MMR-IHC and MSI-polymerase chain reaction for gastroesophageal and small bowel cancer, and only MMR-IHC for endometrial cancer. No recommendation in favor of any testing method over another could be made for any other cancer. Tumor mutational burden was not recommended as a surrogate for DNA MMR deficiency. If MMR deficiency consistent with Lynch syndrome is detected, it should be communicated to the treating physician.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.
Removal of the vicinal disulfide enhances the platelet-capturing function of von Willebrand factor
Authors: Alexander Tischer, Laurie Moon-Tasson, Matthew Auton
Journal: Blood (2023)

Abstract A redox autoinhibitory mechanism has previously been proposed, in which the reduced state of the vicinal disulfide bond in the von Willebrand factor (VWF) A2 domain allows A2 to bind to A1 and inhibit platelet adhesion to the A1 domain. The VWF A1A2A3 tridomain was expressed with and without the vicinal disulfide in A2 (C1669S/C1670S) via the atomic replacement of sulfur for oxygen to test the relevance of the vicinal disulfide to the physiological platelet function of VWF under shear flow. A comparative study of the shear-dependent platelet translocation dynamics on these tridomain variants reveals that the reduction of the vicinal disulfide moderately increases the platelet-capturing function of A1, an observation counter to the proposed hypothesis. Surface plasmon resonance spectroscopy confirms that C1669S/C1670S slightly increases the affinity of A1A2A3 binding to glycoprotein Ibα (GPIbα). Differential scanning calorimetry and hydrogen-deuterium exchange mass spectrometry demonstrate that reduction of the vicinal disulfide destabilizes the A2 domain, which consequently disrupts interactions between the A1, A2, and A3 domains and enhances the conformational dynamics of A1-domain secondary structures known to regulate the strength of platelet adhesion to VWF. This study clarifies that the reduced state of the A2 vicinal disulfide is not inhibitory but rather slightly activating.
Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage–Myofibroblast Transition in Bladder Remodeling
Authors: Wei Wang, Dexuan Xiao, Lede Lin, Xiaoshuai Gao, Liao Peng, Jiawei Chen, Kaiwen Xiao, Shiyu Zhu, Jixiang Chen, Fuxun Zhang, Yang Xiong, Huiling Chen, Banghua Liao, Liang Zhou, Yunfeng Lin
Journal: Advanced Healthcare Materials (2023)

Abstract Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long‐term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO‐induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO‐induced remodeling is aimed. Four single‐strand DNAs are self‐assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF‐ β 1)‐induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO‐induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage–myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF‐ β 1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO‐induced remodeling.